The overall goal of this proposal is to determine whether the estimated prevalence, of Raynaud phenomenon (RP) and of RP associated scleroderma spectrum disorders (SDS) derived from the current project, are peculiar to South Carolina or have more general validity, and more specifically to test the hypotheses that 1) RP is more prevalent in cold regions than in South Carolina, 2) cold is one of the etiological agents, not only a triggering factor for RP, 3) the increased prevalence (and severity) of primary RP in cold climates accounts for most of the difference in RP prevalence between cold and warm regions, 4) capillary microscopy can detect those RP subjects at risk for SDS and 5) subjects with early SDS are several times more numerous in the population than those with classical SD. Using the same criteria and methodology, the work will be carried out in South Carolina and in Haute Savoie, Isere and Drome, France, thus allowing comparisons between cold (Haute Savoie, Isere) and warm (Drome) areas within the same country and between countries (Drome, South Carolina) with comparable climates but different populations. The common specific aims are: Phase I: Population survey by telephone regarding cold sensitivity followed by face-to-face interview of all cold sensitivity positive and a random sample of cold sensitivity negative subjects, using our newly developed RP screening test. Phase II: Extended RP interview and short medical history to detect risk factors and major disorders, confirmation of RP diagnosis and differential diagnosis with acrocyanosis, and detection of RP subjects at risk for SDS by capillary microscopy. Phase III: Clinical evaluation and laboratory studies to determine health status and associated diseases in RP subjects and in negative controls. Blood sample, for immunological studies. Phase IV: Physiological and microvascular studies contrasting survey subjects with different RP subtypes. Phase V: Prospective cohort study of subjects with RP alone or with early SDS disorders. In addition, selected groups of patients, with RP alone, RP with early SDS and definite SD will be examined in the same manner and compared with similar diagnostic groups in the Survey (Case control study). The following experimental variables will be studied: capillary morphology, capillary blood flow, digital blood pressure, digital blood flow, antinuclear antibodies. The results of this study will provide information regarding regional variations in the prevalence of RP, the differences in SDS prevalence and the relative importance of these disorders among the RP subjects from different regions and the usefulness of capillary microscopy for the early detection of SDS disorders.